Apoptosis is an active biological process of elimination, by fragmentation, of certain cells of the organism.
It constitutes a programmed elimination of cells at the biological tissue level, under genetic control. The elimination may be natural (surplus cells in the tissue) or induced by various forms of stress.
The biological cascade of apoptosis is known and uses a number of effectors such as caspases, in particular the effector caspases 3 or 7, which will implement the apoptosis programme, and the initiating caspases 8 and/or 9, which will trigger it.
A certain number of apoptosis inhibitors are also known (Deveraux et al., Genes Dev. 13 (1999), pp. 239-252), among which is survivin. These inhibitors therefore regulate cell survival, thus participating in cell homeostatis in biological tissues.
Survivin, the only member of the IAP (Inhibitor of Apoptosis Protein) family, is a bifunctional protein capable both of balancing the apoptosis of cells and of regulating the cell cycle thereof.
Survivin inhibits in particular the activation of certain caspases, in particular caspases 3, 7 and 9.
This protein is expressed in strongly growing embryonic tissues, but is not expressed in adult differentiated tissues, except in tissues that have a physiological cell renewal and/or are involved in a repair process. Thus, at the cutaneous level, it is most particularly expressed in the keratinocytes of the basal layer of the epidermis, which provide formation and renewal of the latter.
It is in this basal layer that the epidermal stem keratinocytes are found, these being cells with a high potential for regeneration of this tissue, which have been demonstrated to be the most effective in forming a complete epidermis (J L Xie et al., J Plast Reconstr. Aesthet. Surg. 2007; 60(9); 983-90).
Now, it has been shown that survivin is mainly expressed in the stem cells of the epidermis (Marconi A, Dallaglio K, Lotti R, Vaschieri C, Truzzi F, Fantini F, Pincelli C, Stem cells 2007: 25: 149-155).
Conversely, overexpression of survivin shows a significant decrease in the number of apoptotic cells in the epidermis after exposure to ultraviolet radiation (Grossman et al., 2001 J Clin Invest 108; 991-999).
It has also been demonstrated that the inactivation of beta-1 integrins completely abolishes the cellular expression of survivin (Marconi A et al., Stem cells 2007: 25: 149-155) and leads the cells to apoptosis.
Beta-1 integrins are adhesion proteins through which the keratinocytes of the epidermal basal layer adhere to the proteins of the dermal-epidermal junction.
Beta-1 integrins are expressed more strongly by the stem cells of the epidermis (P. Jones, Cell 1993, 73: 713-724, Kaur J Invest Dermatol 2006, 126, 1450-1458), which corroborates the observation of a stronger expression of survivin in these cells.
Now, during ageing, a drop in the expression of beta-1 integrins in the keratinocytes (B Le Varlet et al. J Investig Dermatol Symp Proc. 1998, 3; 172-179) and in the wrinkled skin areas exposed to light (S Bosset et al. British J Dermatol 2003, 148; 7770-778) is observed.
Thus, the proteins which ensure maintenance of survivin in the basal cells of the epidermis decrease with age, and, in parallel, an increase in the sensitivity of the cells to apoptosis and a decrease in cycling cells are observed (Zuliani et al., J. Invest. Dermatol. 2004, 123:2, A50, 302), these observations converging to indicate a probable survivin deficiency in ageing skin.
In addition to its apoptosis-regulating role, survivin has been identified as a constituent of the “chromosomal passenger complex” which coordinates the chromosomes with the cytoskeleton during mitosis (Vader et al., EMBO reports, 2006, 7, 1, 85-92); it therefore plays an essential role in normal cell division, this division being impaired during ageing with, as a consequence, less renewal of the epidermis, thinning thereof, and the development of wrinkles.
Survivin is therefore a regulator of the survival and of the resistance of keratinocytes; it acts by modulating the sensitivity of apoptosis of the keratinocytes located in the basal layer of the epidermis, including the stem cells. It also regulates their capacity for renewal and for regeneration of the epidermis.
It thus makes it possible to spare the cell stock of the epidermis and to maintain efficient epidermal cell renewal.
Document WO 2006/069192 (GILLETTE Co) discloses the use, in cosmetics, of survivin-inhibiting agents for a hair and body-hair growth reduction effect.
To date, no compounds that act as survivin-expression stimulators have been described for uses in dermatology or cosmetics.
Authors have described the antioxidant and free-radical-scavenging effect of an aqueous extract of Limnophila aromatica administered orally to rats (Kukongviriyapan et al., Biol. Pharm Bull. 2007 30 (4) 661-666).
Authors have studied alcoholic extracts of Limnophila conferta and Limnophila heterophylla, administered orally to rats, and have concluded therefrom that these alcoholic extracts have an advantageous activity in terms of wound healing but no significant activity on a model of acute inflammation (Reddy et al., Int. J. Pharmacognosy (1991), 29, 2 145-153).
However, to date, no data exists concerning the use of plant species belonging to the Limnophila genus, and more particularly the species Limnophila conferta, in the form of the product of any method of extraction, as an active agent in cosmetic or dermatological compositions.